Peralta A O, John R M, Gaasch W H, Taggart P I, Martin D T, Venditti F J
Section of Cardiovascular Medicine and Laser Research Laboratory, Lahey Clinic Medical Center, Burlington, Massachusetts, USA.
J Am Coll Cardiol. 2000 Oct;36(4):1404-10. doi: 10.1016/s0735-1097(00)00833-0.
We sought to study the rate related effects of sotalol on myocardial contractility and to test the hypothesis that the class III antiarrhythmic effect of sotalol has a reverse use-dependent positive inotropic effect in the intact heart.
Antiarrhythmic drugs exert significant negative inotropic effects. Sotalol, a beta-adrenergic blocking agent with class III antiarrhythmic properties, may augment contractility by virtue of its ability to prolong the action potential duration (APD).
In 10 anesthetized dogs, measurements of left ventricle (LV) peak (+)dP/dt and simultaneous endocardial action potentials were made during baseline conditions and after sequential administration of esmolol and sotalol. In addition, electrical and mechanical restitution curves were constructed at a basic pacing cycle length of 600 ms by introducing a test pulse of altered cycle length ranging from 200 ms to 2,000 ms.
In the steady state pacing experiments, sotalol prolonged the APD in a reverse use-dependent manner; such an effect was not seen with esmolol. At cycle lengths exceeding 400 ms, LV (+)dP/dt was significantly higher with sotalol than it was with esmolol. There was a direct relation between APD and LV (+)dP/dt with sotalol (r = 0.46, p < 0.001), but there was no significant relation between APD and LV (+)dP/dt with esmolol (r = 0.27, p = NS). Results in the single beat (restitution) studies were qualitatively similar to the steady state results; APD (at cycle length >400 ms) and LV (+)dP/dt (at cycle length >600 ms) were significantly higher with sotalol than they were with esmolol.
The reverse use-dependent prolongation of APD by sotalol is associated with a positive inotropic effect.
我们试图研究索他洛尔对心肌收缩力的频率相关效应，并验证索他洛尔Ⅲ类抗心律失常作用在完整心脏中具有反向使用依赖性正性肌力作用这一假说。
抗心律失常药物具有显著的负性肌力作用。索他洛尔是一种具有Ⅲ类抗心律失常特性的β肾上腺素能阻滞剂，可能因其延长动作电位时程（APD）的能力而增强收缩力。
对10只麻醉犬，在基础状态下以及依次给予艾司洛尔和索他洛尔后，测量左心室（LV）峰值（+）dP/dt并同步记录心内膜动作电位。此外，通过引入周期长度从200毫秒至2000毫秒不等的测试脉冲，在600毫秒的基础起搏周期长度下构建电和机械恢复曲线。
在稳态起搏实验中，索他洛尔以反向使用依赖性方式延长APD；艾司洛尔未观察到这种效应。在周期长度超过400毫秒时，索他洛尔组的LV（+）dP/dt显著高于艾司洛尔组。索他洛尔组的APD与LV（+）dP/dt之间存在直接关系（r = 0.46，p < 0.001），但艾司洛尔组的APD与LV（+）dP/dt之间无显著关系（r = 0.27，p = 无显著性差异）。单次搏动（恢复）研究的结果在性质上与稳态结果相似；索他洛尔组的APD（周期长度>400毫秒时）和LV（+）dP/dt（周期长度>600毫秒时）显著高于艾司洛尔组。
索他洛尔对APD的反向使用依赖性延长与正性肌力作用相关。
